Enzyme-catalyzed synthesis and absolute configuration of (1S,2R,5S)- and (1R,2S,5R)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile, key intermediates for the preparation of chiral cyclobutane-containing pheromones

doi:10.1016/S0957-4166(00)00101-4

Tetrahedron: Asymmetry

Volume 11, Issue 8, 5 May 2000, Pages 1691-1695

https://doi.org/10.1016/S0957-4166(00)00101-4 Get rights and content

Abstract

Formal synthesis of chiral grandisol and the oleander scale pheromone and their antipodes can be achieved through a convenient lipase-catalyzed enantiodifferentiation process of the common cyclobutane intermediate (±)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile 3. The resolution afforded both enantiomers in almost enantiomerically pure form and their absolute configurations were assigned on the basis of the Δδ values for their (R)- and (S)-MTPA esters.

Section snippets

Acknowledgements

Financial support was provided by CICYT (projects AGF95-0185, AGF97-1217-C02-01) and Comissionat per a Universitats i Recerca (1997SGR-00021). We gratefully acknowledge Kenogard for a fellowship to I.P.

References (17)

Thomas, A. F.; Bessière, Y. In The Total Synthesis of Natural Products; Apsimon, J., Ed. The synthesis of monoterpenes,...
Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon Press: New York,...
Bisacchi, G. S.; Braitman, A.; Cianti, C. W.; Clark, J. M.; Field, A. K.; Hagan, M. E.; Hockstein, D. R.; Malley, M....
Bloor, S. J. Tetrahedron Lett. 1993, 34,...
Tumlinson, J. H.; Hardee, D. D.; Gueldner, R. C.; Thompson, A. C.; Hedin, P. A.; Minyard, J. P. Science 1969, 166,...
(a) Einhorn, J.; Guerrero, A.; Ducrot, P. H.; Boyer, F. D.; Gieselmann, M.; Roelofs, W. Proc. Natl. Acad. Sci. USA...
Stork, G.; Cohen, J. F. J. Am. Chem. Soc. 1974, 96,...
Rossini, G.; Marotta, E.; Raimondi, A.; Righi, P. Tetrahedron: Asymmetry 1991, 2, 123 and references cited...

There are more references available in the full text version of this article.

Cited by (15)

Recent advances in the total synthesis of cyclobutane-containing natural products
2019, Organic Chemistry Frontiers
Complex natural products bearing strained cyclobutane subunits, including terpenoids, alkaloids and steroids, not only display fascinating architectures, but also show potent biological activities. Due to their unique structures as critical core skeletons in these molecules, a variety of new strategies for the construction of cyclobutane rings have greatly emerged during the last decade. In this review, we wish to summarize the recent progress in the cyclobutane-containing natural product synthesis with an emphasis on disconnection tactics employed to forge the four-membered rings, aiming to provide a complement to existing reviews.
Synthesis of rumphellaone A via epoxy nitrile cyclization
2012, Tetrahedron
A highly stereocontrolled formal total synthesis of (±)- and of (-)-grandisol by 1,4-conjugated addition of organocopper reagents to cyclobutylidene derivatives
2007, Tetrahedron
Citation Excerpt :
In summary, we have reported two different approaches for a formal total synthesis of racemic grandisol and of the enantiopure (−)-grandisol 1 through the intermediary of cyclobutylidene derivatives. Moreover, as the other diastereoisomer of 9 has been prepared enantiomerically enriched,13 both isomers of grandisol can be prepared using this synthetic approach. Research is now in progress to apply this method to the synthesis of fragranol and to the pheromone of the A. nerii.
Starting from suitable cyclopropanes, a formal total synthesis of racemic grandisol and of the enantiopure (−)-grandisol is presented. The racemic synthesis of the grandisol precursor was accomplished in five steps. The synthesis of the chiral non-racemic precursor (1S,2S,2′R)-cis of this pheromone was realized in 10 steps, with an overall yield of 45%, using the enantiopure cyclobutanone (R,S), previously obtained by ring expansion of an optically pure oxaspiropentane. The key stereodefining step was the addition of lithium dimethylcuprate to a chiral α,β-unsaturated cyclobutylidene carbonyl derivative.
Stereospecific palladium(0)-catalyzed reduction of 2-cyclobutylidenepropyl esters. A versatile preparation of diastereomeric monoterpenoids: (±)-fragranol and (±)-grandisol
2003, Tetrahedron
Mixtures of (E and Z)-2-cyclobutylidenepropyl sulfonates, readily available from α,α-disubstituted cyclobutanones arising from suitable cyclopropane derivatives ring expansion, underwent regioselective and stereospecific reduction by formate anion to offer, through π-1,1-trimethyleneallylpalladium complexes formed upon treatment with palladium(0), a new and convenient entry to the diastereomeric four-membered ring monoterpenoids (±)-fragranol and (±)-grandisol.
An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases
2000, Tetrahedron Asymmetry
Citation Excerpt :
A number of reports have been found in the literature to obtain optically active halohydrins. They comprise enantioselective oxazaborolidine,12 borane13 or microbial reduction14 of α-haloketones, enantioselective hydrolysis of α-halo acetates,15 and resolution of halohydrins by acetylation.16 In our case, bromoalcohol (RS)-4 was subjected to an enzyme-directed enantiodifferentiation process by treatment with some commercially available lipases.
The potent β₂-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described.
Chemistry of the pheromones of mealybug and scale insects
2015, Natural Product Reports

View all citing articles on Scopus

View full text